New drug helps some bald patients regrow hair

August 19, 2014

Drug hairAug 19: The first thing Brian H noticed was that he could grow a real beard. It had been years since that had been possible, years he spent bedevilled by hair loss on his head, face, arms and legs.

Brian, 34, who asked that his last name be withheld to protect his privacy, suffers from alopecia areata, an autoimmune disease afflicting about 1 percent of men and women, causing hair to fall out, often all over the body. He believes that the "mangy patches" of baldness that have plagued him since his 20s have cost him jobs and relationships.

After trying various treatments, Brian enrolled this year in a study at Columbia University Medical Center testing whether a drug approved for a bone marrow disorder could help people with alopecia. One of the study's leaders, Dr Angela Christiano, is a dermatology professor and geneticist who herself has alopecia areata.

After successfully testing on mice, two drugs from a new class of medicines called JAK inhibitors, which suppress immune system activity by blocking certain enzymes, the researchers began testing one of the drugs, ruxolitinib, on seven women and five men. Some of their findings were published Sunday in the journal Nature Medicine.

The results for Brian and several other participants have been significant.

"Pretty quickly, there were sort of fringes," Brian said. Then "three or four large areas started to show hair growth," and by five months, he had plenty of hair on his head, arms, and even his back. "I was blown away," he said.

The disease differs from other types of hair loss, including male pattern baldness, and there is no evidence the drug will work for those conditions. Experts caution that even for alopecia areata, it is too early to know if the treatment will work for most patients and if there are significant side effects or safety concerns.

The study is continuing, but so far a few participants did not regrow hair, said Dr. Julian Mackay-Wiggan, director of Columbia's dermatology clinical research unit and an author of the study.

"It appears to work — not in everyone, but in the majority," she said. "We need a lot more data on the long-term risks in healthy individuals. But it's certainly very exciting in terms of hair growth. It was surprising how quickly and impressively the growth occurred."

Undated handout photos of hair regrowth over time on the head of a patient with alopecia areata taking a drug called ruxolitinib during during a clinical study (NYT photo)

Dr Luis Garza, a dermatologist at Johns Hopkins Hospital who was not involved in the research, said the results were encouraging enough that he would consider prescribing ruxolitinib to patients who could not be treated with other methods and who understood potential side effects.

Cortisone injections often work for patients with isolated patches of baldness, but they must be done regularly and are painful. For patients with severe baldness, "it's impossible to inject their whole scalp", he said.

"There's a major need for improving the treatment," he added. "It's not ludicrous to try on a patient."

But Dr George Cotsarelis, a dermatologist at the University of Pennsylvania, urged caution until further research is conducted. He said it makes sense that drugs suppressing immune system activity would work for a disorder caused by an overly active immune reaction.

But because patients in the study received twice-daily pills that circulated ruxolitinib throughout their bodies, rather than topical cream, he said they were "treated systemically with a very toxic drug" that can cause liver and blood problems, infections and other ailments.

Although the patients have experienced few side effects, the study is small and not a randomized trial comparing ruxolitinib to other treatments.

If ruxolitinib could be applied topically, Cotsarelis said, "This would be an amazing breakthrough." Until then, "patients are going to rush in demanding this treatment, and I would not give it".

Dr Raphael Clynes, a co-leader of the research while he was a Columbia professor (he now works for Bristol-Myers Squibb), said the team tested cream and pills on mice, and planned to test a cream on people.

So far he considered ruxolitinib "an expensive therapy that's probably effective based on the small number of patients that we've treated, and it's likely to have a reasonable safety profile. But there's no way that I can endorse it fully unless we do larger trial."

The team also plans to test on people another JAK inhibitor, tofacitinib, which is approved for rheumatoid arthritis and grew hair on mice. In June, Dr Brett King, a dermatologist at Yale, reported that tofacitinib caused full hair growth and no negative effects for a man with alopecia universalis, a variant involving almost total hair loss.

The idea to use JAK inhibitors grew out of a genome analysis Christiano conducted, which found that in alopecia areata, hair follicles emit a signal that draws immune cells to attack. Her team identified specific cells involved and found genetic similarities to unrelated autoimmune diseases, like rheumatoid arthritis.

Several of the 12 patients are still completing the study, taking ruxolitinib for three to six months. Christiano has not tried it because, she said, her alopecia has been dormant, although "I have an eyebrow that comes and goes."

For Brian, five months on the drug yielded a full head of hair. For unknown reasons, the new hair is white instead of black, its original colour.

Still, "It's a lot easier to shrug that off than to pass the silent judgment of people" who he felt were staring at his bald splotches, he said. He said side effects, including slight anemia, were minor.

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Agencies
January 26,2020

High-protein diets may help people lose weight and build muscle, but there is a downside to it --a greater heart attack risk. Researchers now report that high-protein diets boost artery-clogging plaque.

The research in mice showed that high-protein diets spur unstable plaque -- the kind most prone to rupturing and causing blocked arteries.

More plaque buildup in the arteries, particularly if it's unstable, increases the risk of heart attack.

"There are clear weight-loss benefits to high-protein diets, which has boosted their popularity in recent years," said senior author Babak Razani, associate professor at Washington University School of Medicine in St. Louis, Missouri.

"But animal studies and some large epidemiological studies in people have linked high dietary protein to cardiovascular problems. We decided to take a look at whether there is truly a causal link between high dietary protein and poorer cardiovascular health," Razani added.

The researchers studied mice who were fed a high-fat diet to deliberately induce atherosclerosis, or plaque buildup in the arteries.

Some of the mice received a high-fat diet that was also high in protein. And others were fed a high-fat, low-protein diet for comparison.

The mice on the high-fat, high-protein diet developed worse atherosclerosis -- about 30 per cent more plaque in the arteries -- than mice on the high-fat, normal-protein diet, despite the fact that the mice eating more protein did not gain weight, unlike the mice on the high-fat, normal-protein diet.

"A couple of a scoop of protein powder in a milkshake or smoothie adds something like 40 grams of protein -- almost equivalent to the daily recommended intake," Razani said.

"To see if protein has an effect on cardiovascular health, we tripled the amount of protein that the mice receive in the high-fat, high-protein diet -- keeping the fat constant. Protein went from 15 per cent to 46 per cent of calories for these mice".

Plaque contains a mix of fat, cholesterol, calcium deposits and dead cells. Past work by Razani's team and other groups has shown that immune cells called macrophages work to clean up plaque in the arteries.

But the environment inside plaque can overwhelm these cells, and when such cells die, they make the problem worse, contributing to plaque buildup and increasing plaque complexity.

"In mice on the high-protein diet, their plaques were a macrophage graveyard," Razani informed.

To understand how high dietary protein might increase plaque complexity, Razani and his colleagues also studied the path protein takes after it has been digested -- broken down into its original building blocks, called amino acids.

"This study is not the first to show a telltale increase in plaque with high-protein diets, but it offers a deeper understanding of the impact of high protein with the detailed analysis of the plaques," said Razani.

"This work not only defines the critical processes underlying the cardiovascular risks of dietary protein but also lays the groundwork for targeting these pathways in treating heart disease," he added.

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Agencies
May 14,2020

COVID-19 mostly kills through an overreaction of the immune system, whose function is precisely to fight infections, say scientists who have decoded the mechanisms, symptoms, and diagnosis of the disease caused by the SARS-Cov-2 coronavirus.

In a study published in the journal Frontiers in Public Health, the researchers explained step-by-step how the virus infects the airways, multiplies inside cells, and in severe cases causes the immune defences to overshoot with a "cytokine storm".

This storm is an over-activation of white blood cells, which release too-great amounts of cytokines -- inflammation-stimulating molecules --into the blood, they said.

"Similar to what happens after infection with SARS and MERS, data show that patients with severe COVID-19 may have a cytokine storm syndrome," said study author Daishun Liu, Professor at Zunyi Medical University in China.

"The rapidly increased cytokines attract an excess of immune cells such as lymphocytes and neutrophils, resulting in an infiltration of these cells into lung tissue and thus cause lung injury," Liu said.

The researchers explained that the cytokine storm ultimately causes high fever, excessive leakiness of blood vessels, and blood clotting inside the body.

It also causes extremely low blood pressure, lack of oxygen and excess acidity of the blood, and build-up of fluids in the lungs, they said.

The researchers noted that white blood cells are misdirected to attack and inflame even healthy tissue, leading to failure of the lungs, heart, liver, intestines, kidneys, and genitals.

This multiple organ dysfunction syndrome (MODS) may worsen and shutdown the lungs, a condition called acute respiratory distress syndrome, (ARDS), they said.

This, the researchers explained, happens due to the formation of a so-called hyaline membrane -- composed of debris of proteins and dead cells -- lining the lungs, which makes absorption of oxygen difficult.

Most deaths due to COVID-19 are therefore due to respiratory failure, they said.

The researchers explained that in the absence of a specific antiviral cure for COVID-19, the goal of treatment must be to the fight the symptoms, and lowering the mortality rate through intensive maintenance of organ function.

For example, an artificial liver blood purification system or renal replacement therapy can be used to filter the blood through mechanical means, they said.

The team noted that especially important are methods to supplement or replace lung function, for example with non-invasive mechanical ventilation through a mask, ventilation through a tube into the windpipe, the administration of heated and humidified oxygen via a tube in the nose, or a heart-lung bypass.

The researchers stressed the importance of preventing secondary infections.

They noted that SARS-Cov-2 also invades the intestines, where it causes inflammation and leakiness of the gut lining, allowing the opportunistic entry of other disease-causing microorganisms.

The researchers advocate that this should be prevented with nutritional support, for example with probiotics -- beneficial bacteria that protect against the establishment of harmful ones -- and nutrients and amino acids to improve the immune defences and function of the intestine.

"Because treatment for now relies on aggressive treatment of symptoms, preventative protection against secondary infections, such as bacteria and fungi, is particularly important to support organ function, especially in the heart, kidneys, and liver, to try and avoid further deterioration of their condition," Liu added.

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Agencies
May 8,2020

As Europe and the US loosen their lockdowns against the coronavirus, health experts are expressing growing dread over what they say is an all-but-certain second wave of deaths and infections that could force governments to clamp back down.

"We are risking a backslide that will be intolerable," said Dr Ian Lipkin of Columbia University's Center for Infection and Immunity.

Around the world, German authorities began drawing up plans in case of a resurgence of the virus. Experts in Italy urged intensified efforts to identify new victims and trace their contacts. And France, which has not yet eased its lockdown, has already worked up a "reconfinement plan" in the event of a new wave.

"There will be a second wave, but the problem is to which extent. Is it a small wave or a big wave? It is too early to say," said Olivier Schwartz, head of the virus unit at France's Pasteur Institute.

In the US, with about half of the states easing their shutdowns to get their economies restarted and cellphone data showing that people are becoming restless and increasingly leaving home, public health authorities are worried.

Many states have not put in place the robust testing that experts believe is necessary to detect and contain new outbreaks. And many governors have pressed ahead before their states met one of the key benchmarks in the Trump administration's guidelines for reopening -- a 14-day downward trajectory in new illnesses and infections.

"If we relax these measures without having the proper public health safeguards in place, we can expect many more cases and, unfortunately, more deaths," said Josh Michaud, associate director of global health policy with the Kaiser Family Foundation in Washington.

Cases have continued to rise steadily in places such as Iowa and Missouri since the governors began reopening, while new infections have yo-yoed in Georgia, Tennessee and Texas.

Lipkin said he is most worried about two things: the reopening of bars, where people crowd together and lose their inhibitions, and large gatherings such as sporting events, concerts and plays. Preventing outbreaks will require aggressive contact tracing powered by armies of public health workers hundreds of thousands of people strong, which the US does not yet have, Lipkin said.

Worldwide the virus has infected more than 36 lakh people and killed over a quarter-million, according to a tally by Johns Hopkins University that experts agree understates the dimensions of the disaster because of limited testing, differences in counting the dead and concealment by some governments.

The US has recorded over 70,000 deaths and 12 lakh confirmed infections, while Europe has reported over 140,000 dead.

This week, the researchers behind a widely cited model from the University of Washington nearly doubled their projection of deaths in the US to around 134,000 through early August, in large part because of the easing of state stay-at-home restrictions. Newly confirmed infections per day in the US exceed 20,000 and deaths per day are running well over 1,000.

In hard-hit New York City, which has managed to bring down deaths dramatically even as confirmed infections continue to rise around the rest of the country, Mayor Bill de Blasio warned that some states may be reopening too quickly.

"My message to the rest of the country is learn from how much effort, how much discipline it took to finally bring these numbers down and follow the same path until you are sure that it is being beaten back," he said on CNN, "or else, if this thing boomerangs, you are putting off any kind of restart or recovery a hell of a lot longer."

A century ago, the Spanish flu epidemic's second wave was far deadlier than its first, in part because authorities allowed mass gatherings from Philadelphia to San Francisco.

"It is clear to me that we are in a critical moment of this fight. We risk complacency and accepting the preventable deaths of 2,000 Americans each day," epidemiologist Caitlin Rivers, a professor at Johns Hopkins, told a House subcommittee in Washington.

President Donald Trump, who has pressed hard to ease the restrictions that have throttled the economy and thrown more than three crore Americans out of work, pulled back Wednesday on White House plans revealed a day earlier to wind down the coronavirus task force.

He tweeted that the task force will continue meeting indefinitely with a "focus on SAFETY & OPENING UP OUR COUNTRY AGAIN".

Underscoring those economic concerns, the European Union predicted the worst recession in its quarter-century history. And the US unemployment rate for April, which comes out on Friday, is expected to hit a staggering 16 per cent, a level last seen during the Great Depression of the 1930s.

Governors continue to face demands, even lawsuits, to reopen. In Michigan, where armed demonstrators entered the Capitol last week, the Republican-led Legislature sued Democratic Governor Gretchen Whitmer, asking a judge to declare invalid her stay-at-home order, which runs at least through May 15.

In hard-hit Italy, which has begun easing restrictions, Dr Silvio Brusaferro, president of the Superior Institute of Health, urged "a huge investment" of resources to train medical personnel to monitor possible new cases of the virus, which has killed about 30,000 people nationwide.

He said that contact-tracing apps which are being built by dozens of countries and companies are not enough to manage future waves of infection.

German Chancellor Angela Merkel said after meeting with the country's 16 governors that restaurants and other businesses will be allowed to reopen in the coming weeks but that regional authorities will have to draw up a "restriction concept" for any county that reports 50 new cases for every 100,000 inhabitants within a week.

Lothar Wieler, head of Germany's national disease control centre, said scientists "know with great certainty that there will be a second wave" of infections.

Britain, with over 30,000 dead, the second-highest death toll in the world behind the US, plans to extend its lockdown but has begun recruiting 18,000 people to trace contacts of those infected.

In other developments, the US Centers for Disease Control and Prevention said nearly 5,000 coronavirus illnesses and at least 88 deaths have been reported among inmates in American jails and prisons. An additional 2,800 cases and 15 deaths were reported among guards and other staff members.

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